In 2006, GlaxoSmithKline (GSK) elected to change product label warnings for the antidepressant paroxetine (Paxil), advising against the use of this drug by women who are pregnant. This decision was based on preliminary studies which suggested an increase in the risk of cardiovascular malformations among infants exposed to paroxetine in utero. A recent study from the Motherisk Program in Toronto has reported on the outcomes of over 3000 paroxetine-exposed infants.
The authors contacted teratology information services around the world and were able to ascertain 1,174 unpublished cases of first-trimester paroxetine exposure from eight centers. In addition, the group contacted the authors of previously published studies of antidepressant exposure and was able to obtain an additional 2,061 cases from five previously published database studies, including the GlaxoSmithKline study. All of the women included in this report had been taking paroxetine before they conceived and continued to take paroxetine well into the first trimester, so their infants were exposed during the critical period of fetal heart development.
Rates of cardiovascular defects in the teratology information service cohort were 0.7% in the paroxetine-exposed group and 0.7% in the unexposed control group. In the database group, the rate of cardiovascular malformations was found to be 1.5%. The authors hypothesized that rates were higher in the database group because these studies included all diagnosed cardiovascular defects, even if they resolved spontaneously. In contrast, the teratology information services groups typically did not report cardiovascular defects if they resolved. When the data sets from the teratology information services and from the database studies were combined, the mean rate of cardiovascular defects was 1.2% .
With nearly 1,200 cases from teratology information services and over 2,200 cases from previously published database, this study represents the largest documented number of exposures to paroxetine during the first trimester of pregnancy. The rate of cardiovascular defects among paroxetine-exposed infants reported in this study falls well within the incidence of cardiovascular defects observed in the general population and suggests that paroxetine is not associated with an increased risk of cardiovascular birth defects.
Ruta Nonacs, MD PhD
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